The Effect of Adding Magnesium Sulfate to Local Anesthetic in Patients Undergoing Middle Ear Surgery.

BACKGROUND: The use of local anesthesia has been proved to be beneficial in ear surgeries. AIMS: This study was conducted to compare between local anesthesia alone and in combination with magnesium sulphate as an adjuvant in ear operations.
MATERIALS AND METHODS: This prospective study included a total of 164 cases prepared for elective ear surgeries were included. They were divided into two equal groups, group C or control group included cases who received local anesthesia alone, and group M which included cases who received local anesthesia in addition to magnesium sulphate. Ear ring block was performed in all cases. Monitoring of blood pressure, heart rate, and oxygen saturation was performed. Post-operative pain was assessed by visual analogue score. The total analgesic time and total analgesic requirement were recorded. STATISTICAL ANALYSIS: IBM's SPSS statistics (Statistical Package for the Social Sciences) for windows (version 25, 2017) was used for statistical analysis of the collected data. Shapiro-Wilk test was used to check the normality of the data distribution. All tests were conducted with 95% confidence interval. P (probability) value < 0.05 was considered statistically significant. Charts were generated using SPSS' chart builder and Microsoft Excel for windows 2019.
RESULTS: The onset of sensory blockade was significantly earlier in the Mg group. Mg group showed a significant decrease in intraoperative and post-operative analgesic consumption. In addition, the first request for analgesia after operation was markedly delayed in the Mg group compared to controls. Regarding intraoperative VAS, it was significantly lower in the Mg group compared to controls at 15-minute reading. Post-operative VAS was significantly lower in Mg group during the first two hours.
CONCLUSION: Addition of magnesium to local anesthesia causes early onset of sensory blockade, delayed call first for analgesia, and better VAS scores during the early post-operative period. Copyright:

INTRODUCTION

Both local and general anesthesia can be performed during ear surgery. Each type has its advantages and drawbacks. However, the choice of the type of anesthesia depends mainly on surgeon preference.[1]

Although general anesthesia offers more comfort to both patient and surgeon, local anesthesia decreases operative time, improves hemostasis, and allows hearing testing during operation.[2]

Although local anesthetics are extremely beneficial in acute and chronic pain management, this effect is limited by its duration of action and dose-dependent toxicity. Therefore, adjuvants are used in concomitant to these medications to prolong its duration of action and to decrease the need for cumulative doses.[3]

Magnesium sulfate has been investigated for its analgesic properties in multiple clinical situations. It acts as N-methyl-d-aspartate (NMDA) receptor antagonist. Besides, it inhibits voltage-gated calcium channels. Multiple studies have reported that it can decrease postoperative analgesic requirements in a variety of cases.[4]

Intrathecal administration of magnesium sulfate caused significant prolongation of both sensory and motor blocks for 3–27 h during different operations including orthopedics, general, and gynecological surgeries.[5] Coadministration of magnesium sulfate with opioids in spinal analgesia caused significant analgesic effect without any effect on both sensory and motor blocks.[6]

Magnesium sulfate has been used as an adjuvant to bupivacaine in peripheral nerve blocks including intrascalene, axillary, femoral, and supraclavicular nerve blocks. It caused significant prolongation of analgesic duration without reported side effects.[789]

This study was conducted at Mansoura University hospitals aiming to compare between local anesthesia alone and combined with magnesium sulfate in local anesthesia during ear surgery.

PATIENTS AND METHODS

This prospective, double-blinded randomized study was carried out at the Department of Anesthesia and Surgical Intensive Care, Mansoura University, on cases undergoing elective ear surgery. The study was performed during the period between January 2019 and January 2020.

Cases whose age ranged between 20 and 60 years from both genders and having American Society Association (ASA) physical status Grade 1 or 2 were included in the current study. On the contrary, ASA >2, bleeding disorders, neurological deficits, pregnancy, drug allergy, mental retardation, or local inflammation at injection site were causes of exclusion.

Patients were randomly allocated using the closed envelope method into two equal groups – each group included 82 patients. The total volume of anesthetic solution in each group was 10.5 ml.

Control group (Group C): Which included patients who underwent ring block of the ear using 7 mL xylocaine 2% + 3 mL bupivacaine 0.5% + 0.5 cm adrenaline (1:100,000)

Magnesium sulfate group (Group M): Which included patients who underwent ring block of the ear using 6 mL xylocaine 2% + 3 mL bupivacaine 0.5% + 0.5 cm adrenaline (1: 100,000) + 1 mL (100 mg) magnesium sulfate.

All cases were subjected to complete history taking, thorough physical examination, in addition to routine laboratory and radiological investigations. Furthermore, cases were recommended to fast 8 h prior to surgery.

On arrival to the preanesthetic room, all patients were placed in supine position, then a wide bore (18 G) intravenous (i.v.) cannula was inserted into a suitable peripheral vein, and then 5 mL.kg − 1 of normal saline was infused.

All patients were given midazolam 0.02–0.05 mg.kg as a premedication 5 min before giving the block, and a prophylactic antibiotic was given after the sensitivity test had been done.

The needle was inserted subcutaneously behind the auricle just posterior to postauricular sulcus. Aspiration was performed before injection to avoid intravascular injection. About 2–3 mL of the anesthetic solution was injected subcutaneously to infiltrate the whole postauricular area. Then, another 2 mL was injected anteriorly in intertragal notch (the space between the tragus and the antitragus). Finally, ring block of skin of the external auditory canal by injecting few milliliters of the local anesthetic solution in the four-quadrant of the external auditory canal skin just lateral to bony cartilaginous junction.

Monitoring of heart rate (HR), mean arterial pressure (MAP), respiratory rate, and oxygen saturation (SPO2) were performed before performing the block (basal) and continued monitoring intraoperatively every 15 min. The onset of sensory block was assessed by pinprick using the blunt end of a 27G needle every 5 min and its onset was recorded.

The total time of analgesic duration and the first call for rescue analgesia were recorded. The Visual Analogue scale (VAS) was used to assess the degree of pain. VAS graded from 0 to 10, where 0 there is no pain and 10 is worst pain.[10] It was measured at 15, 30, 45, 60, 90, and 120 min during operation and at the 2nd, 4th, 6th, 8th, 12th, 16th, and 24th h postoperatively. Rescue analgesia (25 mg.kg − 1 of fentanyl) was commenced when pain score was 4 or above.

Intraoperative hypotension (systolic blood pressure <100 mmHg or more than 20% decrease in systolic blood pressure >20% of the baseline) was treated with i.v. boluses, dose of ephedrine (5 mg bolus), and crystalloid fluids. Bradycardia was defined as the presence of pulse rate below 50 beats/min, and it was treated with boluses of 0.2–0.5 mg atropine.

Hypoxia was established when SPO2 <90%, and it was treated by supplemental oxygen. Furthermore, allergic reactions were managed by hydrocortisone 100 mg i.v., while nausea and vomiting were controlled by metoclopramide 10 mg i.v.

Sample size calculation

Sample size was calculated using Power Analysis and Sample Size software program (PASS) version 15.0.5 for Windows (2017) (IBM corporation, Armonk, NY, USA) using the results published by Aydil et al. with the intraoperative pain scores evaluated by VAS scale during myringoplasty under local anesthesia as the primary outcome. Aydil et al. reported the intraoperative pain scores evaluated by VAS score for patients undergoing myringoplasty to be 2.86 with a standard deviation of 1.84.[11]

A mean difference of 30% or more was set as the target difference between both the groups. The null hypothesis was the absence of difference between both the groups. A sample size of 74 patients is in each group needed to achieve 80% power using a two-sided two-sample equal-variance t-test with a significance level of 0.05. The expected number of dropouts is 8 patients in each group, so 82 patients will be enrolled into each group. It was illustrated in Flow Chart 1: Flow chart of the study.

Flow Chart 1

Flow chart of the study

Ethical consideration

Informed written consent was obtained from all cases before participating in the study. Besides, the study was approved by the local ethical committee with a reference number R.20.06.915 at September 16, 2020.

Statistical analysis

IBM's Statistical Package for the Social Sciences (SPSS) statistics for Windows (version 25, 2017) (IBM corporation, Armonk, NY, USA) was used for statistical analysis of the collected data. Shapiro–Wilk test was used to check the normality of the data distribution. All tests were conducted with 95% confidence interval. P (probability) value <0.05 was considered statistically significant. Charts were generated using SPSS chart builder and Microsoft Excel for Windows 2019. Quantitative variables were expressed as mean and standard deviation while categorical variables were expressed as frequency and percentage. Independent sample t-test and Mann–Whitney test were used for intergroup (between subjects) comparison of parametric and nonparametric continuous data with no follow-up readings respectively. For pair-wise comparison of data (within subjects), the follow-up values were compared to their corresponding basal value using paired samples t-test or Wilcoxon matched-pairs signed-ranks test. Fisher's exact and Chi-square tests were used for intergroup comparison of nominal data using the crosstab function.

RESULTS

Both age and gender were not significantly different between the two groups (P > 0.05). However, the onset of sensory blockade was significantly earlier in the Mg group (9.63 vs. 12.26 min – P < 0.001). Although the duration of operation did not differ between the study groups (P = 0.5), the Mg group showed a significant decrease in intraoperative and postoperative analgesic consumption (P < 0.001). In addition, the first request for analgesia after operation was markedly delayed in the Mg group compared to controls (P < 0.001). These data are illustrated in Table 1.

Table 1

Demographic characteristics, operative details, and postoperative analgesic consumption of the studied patients

	Control group (n=82)	Mg group (n=82)	95% CI	P
Age (years)	56.09±7.17	57.24±6.24	−3.2-0.91	0.27
Gender
Male	55% (45)	49% (40)	−0.21-0.09	0.44
Female	45% (37)	51% (42)
Sensory block onset (min)	12.26±4.72	9.63±3.75	1.31-3.94	<0.001
Surgery duration (min)	133.9±26.75	131.16±24.92	−5.2-10.7	0.5
Intraoperative fentanyl (mg.kg−1)	71.95±32.01	50.61±33.56	11.23-31.45	<0.001
First analgesic request (h)	2.47±1.01	4.01±1.06	−1.86-−1.22	<0.001
Total analgesic consumption during the 1st day (mg.kg−1)	88.72±37.09	51.22±28.84	27.3-47.7	<0.001

Data are expressed as mean and SD or percentage and frequency. 95% CI: 95% CI of the mean difference between both groups. P is significant when <0.05. CI=Confidence interval, SD=Standard deviation

Basal and follow-up HRs did not differ significantly between the two groups (P > 0.05) Table 2 and Figure 1 illustrates these data.

Table 2

Basal and follow-up values of heart rate of both groups

Heart rate	Control group (n=82)	Mg group (n=82)	95% CI	P
Basal	79.90±10.956	77.68±16.960	−2.18-6.62	0.32
15 min	82.34±14.232*	78.54±16.027	−0.87-8.48	0.11
30 min	84.12±12.761*	80.68±15.546*	−0.95-7.83	0.12
45 min	83.09±14.959*	79.89±14.887*	−1.41-7.80	0.17
60 min	83.93±15.089*	79.74±15.156*	−0.48-8.85	0.08
75 min	83.18±16.078	78.75±15.530	−0.58-9.45	0.08
90 min	81.33±16.391	76.19±15.650*	−0.69-10.96	0.08
105 min	82.71±15.144	79.47±14.397	−1.45-7.93	0.17
120 min	80.66±15.276	80.34±14.765	−5.15-5.77	0.91
135 min	82.29±12.689	78.80±14.598	−2.52-9.50	0.25
150 min	83.56±13.298	78.50±14.244*	−2.00-12.11	0.16
180 min	93.60±10.164	87.00±15.595	−11.83-25.03	0.44

*Significant difference compared to the respective basal value. Data are expressed as mean and SD. 95% CI: 95% CI of the mean difference between both groups. P is significant when <0.05. CI=Confidence interval, SD=Standard deviation

Figure 1

Basal and follow-up values of heart rate of both groups

Like HR, the mean arterial blood pressure did not differ significantly between the two groups (P > 0.05). Table 3 and Figure 2 illustrates these data.

Table 3

Basal and follow-up values of mean arterial blood pressure of both groups

MAP	Control group (n=82)	Mg group (n=82)	95% CI	P
Basal	89.71±11.964	88.01±11.422	−1.91-5.30	0.35
15 min	63.00±9.842*	62.46±10.206*	−2.56-3.63	0.73
30 min	63.16±10.580*	62.28±10.180*	−2.32-4.08	0.59
45 min	62.96±10.571*	62.05±10.626*	−2.35-4.18	0.58
60 min	63.23±10.682	62.51±10.052	−2.48-3.92	0.66
75 min	63.23±10.307	63.12±10.579	−3.11-3.33	0.95
90 min	63.22±9.970	62.41±9.988	−2.27-3.88	0.61
105 min	63.32±9.881	62.54±10.646	−2.49-4.03	0.64
120 min	63.41±10.721	62.90±10.506	−3.34-4.37	0.79
135 min	61.95±11.167	63.54±10.306	−6.31-3.14	0.51
150 min	62.22±11.084	61.46±10.128	−4.75-6.27	0.78
180 min	61.80±23.952	57.83±9.453	−19.94-27.87	0.72

*Significant difference compared to the respective basal value. Data are expressed as mean and SD. 95% CI: 95% CI of the mean difference between both groups. P is significant when <0.05. CI=Confidence interval, MAP=Mean arterial pressure, SD=Standard deviation

Figure 2

Basal and follow-up values of mean arterial pressure of both groups

Regarding intraoperative VAS, it was significantly lower in the Mg group compared to controls at 15-min reading (P < 0.001). The subsequent intraoperative readings were not significant between the two groups (P > 0.05). When it comes to postoperative VAS, it was significantly lower in the Mg group during the first 2 h (P < 0.001). Nevertheless, other readings were not significantly different between the two groups (P > 0.05). These data are illustrated in Table 4 and Figure 3.

Table 4

Intra- and postoperative Visual Analog Scale of both groups

VAS	Control group (n=82)	Mg group (n=82)	95% CI	P
Intraoperative (min)
15	1 (0, 1)	0 (0, 1)	0.24-0.62	<0.001*
30	1 (1-1)	1 (0-1)	−0.03-0.25	0.116
45	1 (0-1)	1 (0-1)	−0.09-0.21	0.410
60	1 (0-1)	1 (0-1)	−0.27-0.03	0.103
90	1 (0-1)	1 (0-1)	−0.12-0.17	0.743
120	1 (0-1)	1 (0-1)	−0.16-0.14	0.872
Postoperative (h)
2	4 (4-4)	2 (1-2)	2.21-2.62	<0.001*
4	3 (2-3)*	3 (2-3)	−0.33-0.18	0.600
8	3 (2-3)	3 (2-4)	−0.52-0.13	0.210
12	3 (2-4)	3 (2-3)	−0.29-0.41	0.635
16	3 (2, 3.25)*	3 (2-3)	−0.18-0.47	0.408
24	3 (2-3)*	3 (2-3)	−0.11-0.47	0.243

*Significant difference compared to the respective basal value. Data are expressed median and IQR. 95% CI: 95% CI of the mean difference between both groups. P is significant when <0.05. CI=Confidence interval, VAS=Visual analog scale, IQR=Interquartile range

Figure 3

Intra- and postoperative Visual Analog Score of both groups

DISCUSSION

It was previously reported that adding magnesium to local anesthetics causes prolongation of peripheral nerve blockade. It was previously used with bupivacaine, prilocaine, and levobupivacaine. MgSO4 modulates the influx of calcium through acting on NMDA receptors.[3] Moreover, it was also reported that it increases the action of lidocaine via increasing A-beta fiber threshold in animals.[12]

The main advantage of MgSO4 compared to other adjuvants is that the previous studies did not report serious side effects with its use. Lee et al. reported that nausea occurred when higher dose of magnesium was administered (200 mg.kg − 1).[13]

This study was conducted at Mansoura University hospitals aiming to compare between local anesthesia alone and in combination with magnesium sulfate as an adjuvant in ear operations. To the best of our knowledge, this is the first study to assess the role of magnesium sulfate as an adjuvant to local anesthesia in ear surgeries.

There was no significant difference between the two groups regarding patient characteristics (age and sex) (P > 0.05).

This comes in line with the results reported by Ammar and Mahmoud who reported no significant difference between cases in both the groups regarding the same parameters (P > 0.05).[14]

In our study, magnesium sulfate caused significantly earlier sensory block compared to controls (9.63 vs. 12.26 min – P < 0.001).

Our findings are consistent with the findings reported by Ekmekci et al. who reported that the onset of blockade was significantly earlier with using magnesium sulfate (5.8 vs. 8.7 min for controls – P = 0.012).[15]

In another study, the authors did not report any significant difference between the two groups regarding the onset of sensory block (P = 0.45). However, it was earlier in the Mg group (12.5 vs. 14.3 min for bupivacaine alone).[14]

Other results confirmed that the onset of sensory and motor block was significantly more rapid in the magnesium group (7.9 and 10.8 min) than in the control (11.7 and 16.2 min) and tramadol groups (18.2 and 23.4 min).[16]

In the current study, there was no significant difference between the two groups regarding HR or MAP.

Another study has also reported no significant difference between the two groups regarding HR and MAP (P = 0.233 and 0.07, respectively).[17]

In our study, the addition of MgSO4 to local anesthetic was associated with a significant decrease in intraoperative and postoperative fentanyl requirements (P < 0.001). Moreover, the first call for analgesia was markedly delayed in the Mg group compared to controls.

Other authors confirmed our findings as the amount of morphine consumed during the first 2 days after surgery was significantly decreased when using Mg with bupivacaine (16.2 vs. 29.5 mg – P = 0.1).[14]

Another study has reported that total opioid consumption was markedly decreased with MgSO4 coadministration (P = 0.019). The total amount administered had a mean of 391.8 and 558.8 mg in the magnesium and control groups, respectively.[15]

A previous meta-analysis has reported that adding magnesium sulfate to local anesthesia caused significant prolongation of sensory and motor blocks. In addition, a longer period of analgesia was observed during the postoperative period. The incidence of nausea and vomiting did not differ between the MgSO4 and control groups.[18]

Koinig et al. have reported that the combination of preoperative (50 mg.kg) and postoperative (8 mg.kg, h) magnesium infusions decreases both intraoperative and postoperative analgesic requirements.[19]

In the current study, the recorded VAS scores revealed that the MgSO4 group had significantly lower scores at 15 min intraoperatively and 2 h after operation (P < 0.001). The subsequent readings did not differ significantly between the two groups (P > 0.05).

In another study, the Mg group reported significantly lower VAS scores compared to the control group during the first 36 h after operation.[14]

Another study reported that the mean postoperative VAS was significantly lower in the MgSO4 group (mean = 55.1) compared to controls (mean = 81.9) (P = 0.001).[15]

Conversely, Birbicer et al. reported no significant difference after adding MgSO4 (50 mg) to caudal anesthesia in pediatrics.[20] This may be due to the small dose of magnesium used in that study.

In our study, no serious intra- or postoperative complications were encountered. Another study reported that nausea was detected in 12% of cases with MgSO4. However, this was not significantly different from the other group (P = 0.35).[14]

CONCLUSION

Based on our results, the addition of magnesium to local anesthesia causes early onset of sensory blockade, delayed call first for analgesia, and better VAS scores during the early postoperative period.

Financial support and sponsorship

This study was financially supported by the Mansoura University Hospital, Faculty of Medicine.

Conflicts of interest

There are no conflicts of interest.